The current retrospective study involving a total of 1607 patients was designed to identify clinical and molecular variables that were predictive of inferior myelofibrosis-free survival (MFS) in WHO-defined essential thrombocythemia (ET), utilizing three independent patient cohorts: University of Florence, Italy (n = 718); Mayo Clinic, USA (n = 479) and Policlinico Gemelli, Catholic University, Rome, Italy (n = 410). The Florence patient cohort was first examined to identify independent risk factors for MFS, which included age > 60 years (HR 2.5, 95% CI 1.3–4.9), male sex (2.1, 1.2–3.9), palpable splenomegaly (2.1, 1.2–3.9), CALR 1/1-like or MPL mutation (3.4, 1.9–6.1) and JAK2V617F variant allele frequency > 35% (4.2, 1.6–10.8). Subsequently, an operational molecular risk category was developed and validated in the other two cohorts from Mayo Clinic and Rome: “high molecular risk” category included patients with JAK2V617F VAF >35%, CALR type 1/1-like or MPL mutations; all other driver mutation profiles were assigned to “low molecular risk” category. The former, compared to the latter molecular risk category, displayed significantly higher risk of fibrotic transformation: Florence cohort with respective fibrotic transformation risk rates of 8% vs. 1.2% at 10 years and 33% vs. 8% at 20 years (p < 0.001; HR 6.1; 95% CI 3.2–11.7); Mayo Cohort, 16% vs. 7% at 10 years and 44% vs. 25% at 20 years (p < 0.001; HR 2.5; 95% CI 1.6–4.1); and Rome cohort 7.8% vs. 4.6% at 10 years and 31.2% vs. 7.1% at 20 years (p = 0.007, HR 2.7; 95% CI 1.3–5.8). The present study provides practically useful risk signals for fibrotic transformation in ET and facilitates identification of patients who require close monitoring and appropriate counseling.

Clinical and molecular predictors of fibrotic progression in essential thrombocythemia: A multicenter study involving 1607 patients / Loscocco G.G.; Guglielmelli P.; Gangat N.; Rossi E.; Mannarelli C.; Betti S.; Maccari C.; Ramundo F.; Jadoon Y.; Gesullo F.; Ceglie S.; Paoli C.; Pardanani A.; De Stefano V.; Tefferi A.; Vannucchi A.M.. - In: AMERICAN JOURNAL OF HEMATOLOGY. - ISSN 0361-8609. - ELETTRONICO. - 96:(2021), pp. 1472-1480. [10.1002/ajh.26332]

Clinical and molecular predictors of fibrotic progression in essential thrombocythemia: A multicenter study involving 1607 patients

Loscocco G. G.;Guglielmelli P.;Mannarelli C.;Maccari C.;Gesullo F.;Paoli C.;Vannucchi A. M.
2021

Abstract

The current retrospective study involving a total of 1607 patients was designed to identify clinical and molecular variables that were predictive of inferior myelofibrosis-free survival (MFS) in WHO-defined essential thrombocythemia (ET), utilizing three independent patient cohorts: University of Florence, Italy (n = 718); Mayo Clinic, USA (n = 479) and Policlinico Gemelli, Catholic University, Rome, Italy (n = 410). The Florence patient cohort was first examined to identify independent risk factors for MFS, which included age > 60 years (HR 2.5, 95% CI 1.3–4.9), male sex (2.1, 1.2–3.9), palpable splenomegaly (2.1, 1.2–3.9), CALR 1/1-like or MPL mutation (3.4, 1.9–6.1) and JAK2V617F variant allele frequency > 35% (4.2, 1.6–10.8). Subsequently, an operational molecular risk category was developed and validated in the other two cohorts from Mayo Clinic and Rome: “high molecular risk” category included patients with JAK2V617F VAF >35%, CALR type 1/1-like or MPL mutations; all other driver mutation profiles were assigned to “low molecular risk” category. The former, compared to the latter molecular risk category, displayed significantly higher risk of fibrotic transformation: Florence cohort with respective fibrotic transformation risk rates of 8% vs. 1.2% at 10 years and 33% vs. 8% at 20 years (p < 0.001; HR 6.1; 95% CI 3.2–11.7); Mayo Cohort, 16% vs. 7% at 10 years and 44% vs. 25% at 20 years (p < 0.001; HR 2.5; 95% CI 1.6–4.1); and Rome cohort 7.8% vs. 4.6% at 10 years and 31.2% vs. 7.1% at 20 years (p = 0.007, HR 2.7; 95% CI 1.3–5.8). The present study provides practically useful risk signals for fibrotic transformation in ET and facilitates identification of patients who require close monitoring and appropriate counseling.
2021
96
1472
1480
Loscocco G.G.; Guglielmelli P.; Gangat N.; Rossi E.; Mannarelli C.; Betti S.; Maccari C.; Ramundo F.; Jadoon Y.; Gesullo F.; Ceglie S.; Paoli C.; Pardanani A.; De Stefano V.; Tefferi A.; Vannucchi A.M.
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/1257155
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